Detection of human telomerase gene (TERC) amplification in
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Transcript Detection of human telomerase gene (TERC) amplification in
Detection of human telomerase
gene (TERC) amplification in
cervical neoplasia:
A retrospective study of 79 patients Pap
smear slides
Renarta Crookes
Sheffield Children's NHS Foundation Trust
Cervical Cancer
Papanicolou test reduced mortality rate
40,000 cases of mild/moderate
dyskaryosis sent for further investigation
HPV 16 or 18 accounts for 70% of cervical
cancer, majority of mild regress
CGH – Amplification of TERC
CGH – 85% 3q26 TERC
3q26
The RNA component of
the human telomerase
3q gain in interphase
FISH as an indicator
of disease progression?
Categorisation of Smears
Negative
Low Grade
Mild dyskaryosis means the outer 1/3 of the
cervix is affected
High Grade
Moderate dyskaryosis means up to 2/3 of the
skin thickness is affected
CIN3 means the full thickness of the cervical
skin is affected
TERC – A new diagnostic marker?
TERC gain is required for,
and predicts, progression
from mild/moderate
dyskaryosis to CIN3
TERC gain observed in 33%
of negative Pap smears that
progressed to CIN3
100% of mild/moderate
cases that regressed did not
show TERC gains
Heselmeyer-Haddad et al., 2005. Am J. Pathol. 166 1229-1238
The Present Study
Aim – Can FISH for TERC
copy number be used to
improve the current
system for cervical smear
screening?
79 retrospective cases
TERC 3q26
C-MYC 8q24
Negative, mild or moderate progressing
to CIN3 or cervical cancer
Negative, mild or moderate regressing or
remaining negative
Results- Negative progressing to
CIN3
Increase in TERC copy number
Normal diploid cell
x100
x40
Results- Negative progressing to
CIN3
100
90
% of nuceli with
more than two
copies of TERC
80
70
60
50
40
% of nuclei with
more than two
copies of C-MYC
30
20
10
0
A
B
C
D
E
F
G
H
Patient
I
J
K
L
M
N
Results- Mild progressing to
CIN3
Increase in
C-MYC
Increase in TERC
Results- Mild progressing to
CIN3
100
% of nuclei
with more
than two
copies of
TERC
90
80
70
60
50
40
% of nuclei
with more
than two
copies of CMYC
30
20
10
0
A1
B1
C1
D1
E1
F1
G1
H1
Patient
I1
J1
K1
L1
M1
N1
O1
Results- Moderate progressing
to CIN3
82.4%
showed
70.6%
showed
moderate cases
gain of TERC
moderate cases
gain of C-MYC
Results- Moderate progressing
to CIN3
100
% of nuclei
with more
than two
copies of
TERC
90
80
70
60
50
% of nuclei
with more
than two
copies of
C-MYC
40
30
20
10
0
A2
B2
C2
D2
E2
F2
G2
H2
I2
P a t i e nt
J2
K2
L2
M2
N2
O2
P2
Q2
Summary of Progressors
100
90
% of cases
with more
than two
copies of
TERC
80
70
60
50
40
30
% of cases
with more
than two
copies of CMYC
20
10
0
Negative
Mild Dyskaryosis
Moderate
Dyskaryosis
Results- Negative remaining
Negative
100
90
80
% of nuclei with
more than two
copies of TERC
70
60
50
40
% of nuclei with
more than two
copies of C-MYC
30
20
10
0
A
B
C
D
E
F
G
H
Patient
I
J
K
L
M
N
O
Results- Mild regressing to negative
100
90
80
% of nuclei with
more that 2
copies of TERC
70
60
50
40
30
20
% of nuclei with
more than 2
copies of C-MYC
10
0
A1
B1
C1
D1
E1
F1
Patient
G1
H1
I1
J1
Results- Moderate regressing to
negative
100
90
80
% of nuclei with
more than 2
copies of TERC
70
60
50
40
% of nuclei with
more than 2
copies of C-MYC
30
20
10
0
A2
B2
C2
D2
E2
Patient
F2
G2
H2
Regressors
Negative and mild dyskaryosis
patients that regressed or
remained negative showed no
gains in TERC
2/8 patients classed as
moderate dyskaryosis
showed gains of TERC,
with a high proportion of
tetraploid cells.
Summary of Regressors
100
% of cases with
more than two
copies of TERC
90
80
70
60
% of cases with
more than two
copies of C-MYC
50
40
30
20
10
0
Negative
Mild Dyskaryosis
Moderate Dyskaryosis
Study Summary
90 cases received
79 successful analyses
2 insufficient sample to score (min no.
cells to score?)
5 fails in progressors (thick smears)
4 fails in regressors (from 2000 - ?bond)
Application as a service
Analysis of slides ranges from 30 mins to over
an hour by eye per analyser
Automation – Scanning, Capture + Relocation
Liquid based cytology slides – reducing cell
clumping/false positive rate, no de-staining
Conclusions
TERC increases with severity of disease
Both negative and mild dyskaryosis
regressors showed no gains in TERC
Prospective work using liquid based cytology
slides
Trial automation to reduce analysis
Improve detection rate and reduce costs and
patient anxiety
Acknowledgments
Dr John H F Smith
Michael Dyson
Dr Edna L. Maltby
Abbott Vysis
Royal Hallamshire Hospital)
Service)
(Dept. of Histopathology,
(Sheffield Cytogenetics Service)
(Sheffield Cytogenetics